NM_001337.4:c.825C>T

Variant names:

• chr3-39265685-G-A
• rs1575205636
• NM_001337.4:c.825C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001337.4(CX3CR1):​c.825C>T​(p.Leu275Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CX3CR1 NM_001337.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.190
• Publications: 0 publications found

Genes affected

CX3CR1 (HGNC:2558): (C-X3-C motif chemokine receptor 1) Fractalkine is a transmembrane protein and chemokine involved in the adhesion and migration of leukocytes. The protein encoded by this gene is a receptor for fractalkine. The encoded protein also is a coreceptor for HIV-1, and some variations in this gene lead to increased susceptibility to HIV-1 infection and rapid progression to AIDS. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-39265685-G-A is Benign according to our data. Variant chr3-39265685-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 764930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.19 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001337.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CR1	NM_001337.4	MANE Select	c.825C>T	p.Leu275Leu	synonymous	Exon 2 of 2	NP_001328.1	P49238-1
	CX3CR1	NM_001171174.1		c.921C>T	p.Leu307Leu	synonymous	Exon 2 of 2	NP_001164645.1	P49238-4
	CX3CR1	NM_001171171.2		c.825C>T	p.Leu275Leu	synonymous	Exon 2 of 2	NP_001164642.1	P49238-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CR1	ENST00000399220.3	TSL:1 MANE Select	c.825C>T	p.Leu275Leu	synonymous	Exon 2 of 2	ENSP00000382166.3	P49238-1
	CX3CR1	ENST00000358309.3	TSL:2	c.921C>T	p.Leu307Leu	synonymous	Exon 2 of 2	ENSP00000351059.3	P49238-4
	CX3CR1	ENST00000541347.5	TSL:4	c.825C>T	p.Leu275Leu	synonymous	Exon 2 of 2	ENSP00000439140.1	P49238-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.65
PhyloP100		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1575205636; hg19: chr3-39307176;